UCSF-Led Team Decodes Evolution of Skin and Ovarian Cancer Cells

A team of researchers led by scientists at the University of California, San Francisco (UCSF) has developed a way to uncover the evolution of human cancer cells, determining the order in which mutations emerge in them as they wend their way from a normal, healthy state into invasive, malignant masses.

The work may give doctors a new way to design diagnostics for detecting the signs of early cancers, when they are generally more treatable than in their later stages.

This approach relies on teasing apart the DNA of cancer cells, and it is something like genetic archeology. Just as archeologists sometimes date objects found at an excavation site by the age of the objects found around them, the new technique allows scientists to dig into the DNA of cancer cells and determine which genetic mutations came first by looking at surrounding genetic material.

Using the new technique, the researchers were able to identify not just the mutations that differentiate two types of human cancer from normal cells, but the actual order in which some of the most key mutations occurred.

“You can tell which mutations come really early and which come late,” said UCSF dermatologist Raymond Cho, MD, PhD.

Cho and his UCSF colleagues developed the technique in collaboration with researchers led by Paul Spellman and Joe Gray at Oregon Health & Science University, Elizabeth Purdom at the University of California, Berkeley and scientists at Samsung Advanced Institute of Technology. The work appears this week in the journal Cancer Discovery.

Mutations Lead to CancerCancer is a profoundly heterogeneous disease, making it more like thousands of diseases than just one. Different types of cancer differ in terms of the organs they affect, how they behave in the body, how they respond to treatment and even how they look under the microscope. And most fundamentally, they differ genetically.

Cancer emerges because of mutations in the DNA of cells. Any number of things can cause these mutations – for instance, family genetics, infections, toxins, radioactivity, sunlight or some combination of each. Over time these mutations shut down some genes, crank up the production of others and lead in the end to the cell’s proliferation, growth, spread and all the other ominous hallmarks of cancer.